We aim to develop new, general methods for obtaining non-racemic biologically-active molecules using transition metal-catalyzed carbon-carbon bond-forming reactions that employ configurationally-stable, optically-active nucleophiles. By establishing the stereogenic center prior to the formation of the final desired bond, the rapid preparation of diverse libraries of single-enantiomer drug candidates for use in biologic assays will be achievable. The use of optically-active secondary nucleophiles will be initially explored in alkyl-aryl cross-coupling reactions and extended to alkyl-alkyl cross-coupling reactions in order to maximize access to chiral structural motifs that are currently inaccessible but are of biological or pharmaceutical interest. PUBLIC HEALTH RELEVANCE: Our proposed research focuses on the development of new, general methods to prepare diverse libraries of biologically-active molecules for testing as drug candidates. We aim to devise new drug discovery techniques that permit rapid access to common, high- demand molecular architectures predictably, safely, and inexpensively.